The mechanisms by which iron is stored, mobilized, and delivered in the human body are being investigated. Using two radioisotopes of iron, we are studying factors which influence the transfer of iron between ferritin and transferrin. The effect of the heat treatment used in isolating ferritin on the reactivity of the iron core is being examined. EPR spectroscopic labels for the two sites of transferrin were used to study the pH dependence of metal binding. Iron at each site of transferrin was found to be equally available for uptake by human reticulocytes. Using a nitroxyl spin-labelled anion, it was shown that the anion necessary for metal binding by transferrin is directly attached to the metal. Mild conditions for removing iron from transferrin at sub-physiologic pH are being developed with the goal of devising a hemodialysis procedure for removing iron from transfusion-induced iron-overloaded patients.